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Gene editing has many promising applications for the treatment of diseases with unmet clinical needs, including cancers and autoimmune. There are two main routes for gene delivery: viral and non-viral. Recent research shows viral methods are emerging in clinical trials. Nevertheless, there are still a couple of technological obstacles that require further improvements, these include virus concentration and low efficiency of transduction. This research aimed to employ superparamagnetic iron oxide nanoparticles (SPION) to solve these problems. Three sizes of 10, 40, and 120 nm SPION were synthesized by co-precipitation and Sol-Gel methods, and characterized by XRD, FTIR, FESEM, and VSM. Conjugating SPION to viruses by polyethylene glycol (PEG) can increase the sedimentation of viruses due to magnetic and gravity forces even without ultracentrifuge. Moreover, this magnetic force can guide viruses toward cells and tremendously facilitate the transduction process. As shown, average size SPION (40 nm) revealed the best performance, especially in combination with salting-out precipitation and increased transduction efficiency of more than 20-fold. SPION size has significant effects and should be considered for this application. The combination of the salting-out method and SPION has a synergic effect and elevates transduction results tremendously. [ABSTRACT FROM AUTHOR]

Gene delivery systems necessitate the gene therapy, which is a unique approach for applying the tunable genes to treat any diseases. To tackle down the disadvantages of viral vectors like high cost, poor target cell specificity, and inability in transferring the large size genes, the non-viral vectors/carriers have been introduced for achieving better efficacy in gene therapy. A variety of carriers including liposomes, metallic/polymeric nanoparticles, dendrimers, gelatins, quantum dots/rods, etc. has been depicted distinct features in the gene therapy. Herein, the advances and applications of natural/synthetic polymeric carriers have been summarized in gene therapy and disadvantages/challenges have been also discussed. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting. [ABSTRACT FROM AUTHOR]

Nanoparticles recently play remarkable roles in modern agriculture and biotechnology due to specific exclusively physicochemical and biological characteristics of the particles. In recent years, nanoparticles are been using as fertilizers and elicitors to improve crops. Nutritionists are constantly seeking natural antioxidants without side effects to using for healthcare and treatment. Asparagus officinalis L. as medicinal plant treated by iron (0, 10, 50 and 100 mg/L) and selenium (0, 0.5, and 1 mg/L) nanoparticles as nano elicitors. Then the antioxidant capacity of A. officinalis L. was detected and measured by a, a-diphenyl-ß-picrylhydrazyl (DPPH) assay, for assessment of the antioxidant activity. The iron nanoparticles concentration significantly increases the antioxidant activity of both male and female asparagus stem, as well as selenium nanoparticles. When combined iron and selenium used as nano elicitors then cause the antioxidant activity significantly decreases. But the integration of two nano elicitors (iron and selenium) decreased antioxidant capacity while the use of nano-selenium could enhance antioxidant capacity. The application of nano elicitor increased antioxidant capacity in the female stem than male. [ABSTRACT FROM AUTHOR]

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family. [ABSTRACT FROM AUTHOR]

It has been reported that there is an association of lymphopenia to the mortality rate in COVID-19 patients and also there is an association of severe COVID-19 symptoms with lymphocytosis. Maybe the neural damages in COVID-19 patients are inhibited in part using vitamin E consumption through an anti-ferroptosis mechanism. COVID-19 patients suffer from GPX4 depletion, confirming ferroptosis. [Extracted from the article]

OBJECTIVES Open in new tab Download slide Open in new tab Download slide The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation. METHODS Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10–15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years. RESULTS Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications. CONCLUSIONS Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates. [ABSTRACT FROM AUTHOR]

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX. [ABSTRACT FROM AUTHOR]

Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC‐specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients. [ABSTRACT FROM AUTHOR]

In the last decade, the Islamic Republic of Iran has witnessed significant improvement and growth in the field of interdisciplinary medicine and in its translation to patients, including the field of cell and stem cell therapy. The main aim of this report is to highlight various advances in regenerative medicine for skin and dermatology using stem cell technology, and its translation to clinic in the past two decades, in Iranian academic centers, clinical institutes and hospitals. While there have been numerous positive advances in clinical outcomes reported in Iran, there is no comparative analytical information on these studies. Here we present a historical overview of the progress and key advancements seen in skin regeneration in this country, review the research frameworks, regulatory approach and pathways and offer perspectives for the future. [ABSTRACT FROM AUTHOR]

Abstract: We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml−1 and ≥ 4 mg ml−1 for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml−1 and ≥ 4 mg ml−1, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml−1 and ≤ 32 μg ml−1, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml−1. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial. [ABSTRACT FROM AUTHOR]

Introduction: In this research, low-level helium-neon (He-Ne) laser irradiation effects on monkey kidney cells (Vero cell line) mitosis were studied. Methods: The experiment was carried out on a monkey kidney cell line "Vero (CCL-81)". This is a lineage of cells used in cell cultures and can be used for efficacy and media testing. The monolayer cells were formed on coating glass in a spectral cuvette (20×20×30 mm). The samples divided into two groups. The first groups as irradiated monolayer cells were exposed by a He-Ne laser (PolyaronNPO, L'vov, Ukraine) with λ = 632.8 nm, max power density (P) = 10 mW/cm2, generating linearly polarized and the second groups as the control monolayer cells were located in a cuvette protected by a lightproof screen from the first cuvette and also from the laser exposure. Then, changing functional activity of the monolayer cells, due to the radiation influence on some physical factors were measured. Results: The results showed that low-intensity laser irradiation in the range of visible red could make meaningful changes in the cell division process (the mitosis activity). These changes depend on the power density, exposure time, the presence of a magnetic field, and the duration of time after exposure termination. The stimulatory effects on the cell division within the power density of 1-6 mW/(cm2) and exposure time in the range of 1-10 minutes was studied. It is demonstrated that the increase in these parameters (power density and exposure time) leads to destructing the cell division process. Conclusion: The results are useful to identify the molecular mechanisms caused by low-intensity laser effects on the biological activities of the cells. Thus, this study helps to optimize medical laser technology as well as achieving information on the therapeutic effects of low-intensity lasers. [ABSTRACT FROM AUTHOR]

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices. [ABSTRACT FROM AUTHOR]

Bone regeneration is considered as an unmet clinical need, the aim of this study is to investigate the osteogenic potential of three different mesenchymal stem cells (MSCs) derived from human bone marrow (BM-MSCs), umbilical cord Wharton's jelly (UC-MSCs), and adipose (AD-MSCs) seeded on a recently developed nanocomposite scaffold (bioactive glass/gelatin) implanted in rat animal models with critical size calvarial defects. In this study, after isolation, culture, and characterization, the MSCs were expanded and seeded on the scaffolds for in vitro and in vivo studies. The adhesion, proliferation, and viability of the cells on the scaffolds evaluated in vitro, showed that the scaffolds were biocompatible for further examinations. In order to evaluate the scaffolds in vivo, rat animal models with critical size calvarial defects were randomly categorized in four groups and treated with the scaffolds. The animals were sacrificed at the time points of 4 and 12 weeks of post-implantation, bone healing process were investigated. The histological and immunohistological observations showed ( p < 0.01) higher osteogenesis capacity in the group treated with BM-MSCs/scaffolds compared to the other groups. However, the formation of new angiogenesis was evidently higher in the defects filled with UC-MSCs/scaffolds. This preliminary study provides promising data for further clinical trials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 61-72, 2018. [ABSTRACT FROM AUTHOR]

Despite great advances in tissue engineering, there have been very few reports on the successful clinical use of small-diameter tissue-engineered vascular grafts (TEVGs). Small-diameter (<6 mm internal diameter) is considered as unmet clinical need. This review critically examines the role of stem cells that have been proposed and used in development of TEVGs, and assesses the viability of such graft to clinical pathway. With over 20 years of expertise in development of bypass graft and a number of grafts under clinical trial, this team will offer potential areas for future research that may help improve the current state-of-the-art technology. [ABSTRACT FROM AUTHOR]

There has been huge interest in applications of nanomaterials in biomedical science, including diagnosis, drug delivery, and development of human organs. Number of these nanomaterials has been already studied in human or at pre-clinical trial. There is a growing concern on potential toxicity and adverse effects of nanomaterials on human health, including lack of standard method of assessment of toxicology of these materials. Our investigation indicated that the bare and small nanoparticle have higher toxicity than modified and bulk materials, respectively. In addition, spherical nanoparticles have less toxicity than rod nanoparticles due to immune response of body. [ABSTRACT FROM AUTHOR]

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells ( ESC) or induced pluripotent stem cells ( iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells ( ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery. [ABSTRACT FROM AUTHOR]

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly("ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine-glycine-aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31+/CD34+/vWF+ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31+CD34/vWF+ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31+/CD34+ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts. [ABSTRACT FROM AUTHOR]

Whole-organ decellularization and tissue engineering approaches have made significant inroads during recent years. If proven to be successful and clinically viable, it is highly likely that this field would be poised to revolutionize organ transplantation surgery. In particular, whole-heart decellularization has captured the attention and imagination of the scientific community. This technique allows for the generation of a complex three-dimensional (3D) extracellular matrix scaffold, with the preservation of the intrinsic 3D basket-weave macroarchitecture of the heart itself. The decellularized scaffold can then be recellularized by seeding it with cells and incubating it in perfusion bioreactors in order to create functional organ constructs for transplantation. Indeed, research into this strategy of whole-heart tissue engineering has consequently emerged from the pages of science fiction into a proof-of-concept laboratory undertaking. This review presents current trends and advances, and critically appraises the concepts involved in various approaches to whole-heart decellularization and tissue engineering. [ABSTRACT FROM AUTHOR]

In this study, the effects of osteoblast-conditioning on mechanical behavior, biocompatibility, biodegradation and osteoinductive properties of a nano-hydroxyapatite/gelatin (HA/GEL) nanocomposite scaffold was investigated. The scaffold was fabricated using the layer solvent casting combined with the freeze-drying and lamination techniques. The scaffolds were conditioned by culture of osteoblasts on their surface and their elimination by a repeated freeze-thawing process. The potential of the osteoblast-conditioned HA/GEL (HA/GEL/OC) scaffold to support cell adhesion and growth and its cytotoxicity was assessed in vitro using rat mesenchymal stem cells. For in vivo studies, the HA/GEL/OC nanocomposite was implanted in the critical size bone defect created on rat calvarium and studied after 7, 30 and 90 days. The results showed that mechanical and in vitro biological properties of the scaffold were not affected by the process of conditioning. However, in vivo studies demonstrated that osteoblast-conditioning enhanced biocompatibility and osteoinductivity and of the nanocomposite scaffold. The osteoblast conditioning also accelerated collagen content during the bone healing. In the experimental group that received the HA/GEL/OC and MSCs, the newly formed bone occupied almost the entire defect (93.4 ± 3.3%) within 3 months. In conclusion, this study indicates that osteoblast-conditioning is a viable strategy for the development of bone tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2001-2010, 2016. [ABSTRACT FROM AUTHOR]

In the cardiovascular system, the endothelial layer provides a natural antithrombogenic surface on the inner portion of the heart and associated vessels. For a synthetic material therefore, the ability to attract and retain endothelial or endothelial progenitor cells (EPCs), ultimately creating a single endothelial layer on its surface, is of prime importance. The authors have developed a nanocomposite polymer, based on a combination of polyhedral oligomeric silsesquioxane nanoparticles and polycarbonate urea urethane (POSS-PCU), which is biocompatible and has been used in human for the world's first synthetic trachea, tear duct, and bypass graft. In this study, the authors modified the surface of this casted nanocomposite by grafting fibronectin derived bioactive peptides [glycine-arginine-glycine-aspartic acid-glycine (GRGDG) and lauric acid conjugated GRGDG (GRGDG-LA)] to enhance the endothelialization for using heart valves leaflets from circulating EPCs. Human peripheral blood mononuclear cells were separated using Ficoll-Paque centrifugation, with harvested EPCs purified using CD34 microbead labeling and magnetic-activated cell sorting. Cells were seeded onto 96 well plates coated with POSS-PCU, GRGDG/GRGDG-LA modified POSS-PCU and PCU polymers, for a period of 21 days. Cells were studied under light, confocal, and scanning electron microscope (SEM). Fluorescenceactivated cell sorting was used to analyze cell surface markers. Cell attachment and proliferation was observed in all POSS-PCU samples, significantly higher than the activity seen within the control PCU polymers (p<0.05). Microscopic examination revealed clonal expansion and morphological changes in cells seeded on POSS-PCU. The cells expressed increasing levels of mature endothelial cell markers over time with a concurrent reduction in hematopoietic stem cell marker expression. SEM showed a mixed population of morphologically differentiated endothelial cells and EPCs. These results support the use of heart valve made with the POSS-PCU polymer and demonstrate that suitable chemical modification of this nanocomposite could increase self-endothelialization potential and reduce associated thrombotic events. [ABSTRACT FROM AUTHOR]

Small diameter arterial bypass grafts are considered as unmet clinical need since the current grafts have poor patency of 25% within 5 years. We have developed a 3D scaffold manufactured from natural and synthetic biodegradable polymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(+-caprolactone) (PCL), respectively. Further to improve the biophysical properties as well as endothelialisation, the grafts were covalently conjugated with arginine-glycine-aspartic acid (RGD) bioactive peptides. The biophysical properties as well as endothelialisation of PHBV/PCL and PCL 2 mm diameter bypass grafts were assessed with and without biofunctionalisation with RGD peptides in vitro and in vivo. Morphology of the grafts was assessed by scanning electron microscopy, whereas physico-mechanical properties were evaluated using a physiological circulating system equipped with a state of art ultrasound vascular wall tracking system. Endothelialisation of the grafts in vitro and in vivo were assessed using a cell viability assay and rat abdominal aorta replacement model, respectively. The biofunctionalisation with RGD bioactive peptides decreased mean fiber diameter and mean pore area in PHBV/PCL grafts; however, this was not the case for PCL grafts. Both PHBV/PCL and PCL grafts with RGD peptides had lower durability compared to those without; these durability values were similar to those of internal mammary artery. Modification of PHBV/PCL and PCL grafts with RGD peptides increased endothelial cell viability in vitro by a factor of eight and enhanced the formation of an endothelial cell monolayer in vivo 1 month postimplantation. In conclusion, PHBV/PCL small-caliber graft can be a suitable 3D scaffold for the development of a tissue engineering arterial bypass graft. [ABSTRACT FROM AUTHOR]

Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells ( HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane ( POSS- PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS- PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P < 0.001), favorable kink resistance, and excellent suture retention property (casted vs. coagulated, P < 0.05). Cytocompatibility study showed that the POSS- PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue-engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema. [ABSTRACT FROM AUTHOR]

Objective Selection of the appropriate sterilisation method for biodegradable materials has been a challenging task. Many conventional sterilisation methods are not suitable for the next generation of biomaterials, mainly due to their complex composition, based on nanomaterials, often incorporating bioactive moieties. In this study, we investigate sterilisation efficacy of slow chlorine releasing compound sodium dichloroisocyanurate dihydrate (SDIC) for polyhedral oligomeric silsesquioxane (POSS)-poly(caprolactone urea-urethane) (PCL) scaffolds in comparison with conventional sterilisation methods. Methods POSS-PCL scaffolds were subjected to 70% ethanol, UV, and SDIC sterilisation methods. Samples were immersed in tryptone soya broth (TSB) and thioglycollate medium (THY) and after seven days visually inspected for signs of microbial growth. Bulk and surface properties and molecular weight distribution profiles of the scaffolds after sterilization were investigated using FTIR analysis, surface hydrophilicity, scanning electron microscopy analysis, tensile strength testing, and gel-permeation chromatography (GPC). Adipose-derived stem cells (ADSC) were seeded on the scaffolds and AlamarBlue® viability assay was performed to investigate cell metabolic activity. Confocal imaging of rhodamine phalloidin and Dapi stained ADSC on scaffolds was used to demonstrate cell morphology. Results GPC results showed that autoclaving led to a significant decrease in the molecular weight of POSS-PCL, whereas ethanol caused visible deformation of the polymer 3D structure and UV radiation did not effectively sterilise the scaffolds. AlamarBlue® analysis showed metabolic activity close to that of tissue culture plastic for ethanol and SDIC. Conclusion SDIC sterilisation can be safely applied to biodegradable scaffolds unsuitable for the more common sterilisation methods. [ABSTRACT FROM AUTHOR]

Background: There is a great potential for nitric oxide (NO) eluting biomaterials in biomedical applications. These include the development of cardiovascular implants, wound healing products, or applications in cancer and respiratory therapy. While the potential of these materials as a therapy is becoming clearer, the real-time monitoring of NO is not easy and the success in the development of such materials depends on the accurate quantification of NO release. Method: To emphasize on the importance of a measurement technique on the outcome of an experiment, we compared total NO released from S-nitroso-N-acetyl-d-penicillamine (SNAP) incorporated nanocomposite polymer in the form of bypass grafts under simulated physiological conditions using amperometric and chemiluminescence techniques. Results: We found that the total amount of NO measured by the amperometric technique was 35.8% of the theoretical amount. Similarly, on measuring NO release from the bypass grafts, we demonstrated that the chemiluminesence technique detected NO at a relatively higher level. Conclusions: The results of this study clearly demonstrate the relative difference between analysis techniques for accurate NO detection that can be applied to distinct experimental models associated with NO-eluting cardiovascular implants. [ABSTRACT FROM AUTHOR]

Context:Congenital heart disease is a leading cause of death in the first year, with an incidence of 1.5 million worldwide. It can be treated with bypass surgery, but due to the limited availability of autologous grafts, there has been research into developing a completely tissue-engineered vascular graft. Our group has developed a small diameter, biodegradable nanocomposite graft which is non-thrombogenic and biostable.Objectives:This study looks at the effects of the growth factors, TGF-β1 and BMP-4 on bone marrow-derived stem cell (BMSC) morphology on a POSS PCL scaffold.Materials and methods:BMSCs were seeded onto a new nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL (poly[caprolactone-urea]urethane) and TGF-β1 and BMP-4 were used to induce differentiation of the cells to smooth muscle cells. The distribution of the cells was examined using confocal and electron microscopies and the phenotype of the cells was assessed using immunohistochemistry.Results:It was found that growth factor induction led to a decrease in cell growth on POSS PCL as compared to that of the control surface, and confocal microscopic analysis showed less cytoskeleton reorganization of these cells. After immunohistochemistry analysis, the BMSCs showed no differentiation to smooth muscle cells.Discussion:Growth factor induction on the static scaffold discs led to a change in morphology, with less spreading of the cells, a lower proliferation rate and no differentiation into SMCs. These findings can be attributed to the POSS PCL being manufactured by a coagulation technique, resulting in a structure with low stiffness. [ABSTRACT FROM PUBLISHER]

Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content. Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS–PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS–PCL and a new lamination method was explored. Porogen (40, 60 or 105 μm) were introduced to POSS–PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS–PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 lm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS–PCL. These bilayeredtubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored. [ABSTRACT FROM AUTHOR]

The patency of synthetic cardiovascular grafts in the long run is synonymous with their ability to inhibit the processes of intimal hyperplasia, thrombosis and calcification. In the human body, the endothelium of blood vessels exhibits characteristics that inhibit such processes. As such it is not surprising that research in tissue engineering is directed towards replicating the functionality of the natural endothelium in cardiovascular grafts. This can be done either by seeding the endothelium within the lumen of the grafts prior to implantation or by designing the graft such that in situ endothelialisation takes place after implantation. Due to certain difficulties identified with in vitro endothelialisation, in situ endothelialisation, which will be the focus of this article, has garnered interest in the last years. To promote in situ endothelialisation, the following aspects can be taken into account: (1) Endothelial progenital cell mobilization, adhesion and proliferation; (2) Regulating differentiation of progenitor cells to mature endothelium; (3) Preventing thrombogenesis and inflammation during endothelialisation. This article aims to review and compile recent developments to promote the in situ endothelialisation of cardiovascular grafts and subsequently improve their patency, which can also have widespread implications in the field of tissue engineering. [ABSTRACT FROM AUTHOR]